Biology subjects

Toukabri, H.

Publications and source records attributed to Toukabri, H..

3 recordsLinked to original sources

bioRxiv2026

Environmental history shapes host-associated dynamics of sporulating and non-sporulating bacterial subpopulations during infection

Host-associated environments represent ecological contexts that can structure microbial population dynamics, yet their effects on sporulating pathogens remain poorly understood. We investigated how passage through a natural insect host shapes population-level traits in the entomopathogen Bacillus thuringiensis. Using Galleria mellonella larvae, we compared the characteristics of bacterial populations extracted from insect cadavers with those maintained under in vitro conditions. Passage through the host generated a distinct population structure, characterized by the stable coexistence of sporulating and non-sporulating bacteria and a larger non-sporulating fraction than in in vitro cultures. Host-extracted bacteria exhibited a different morphology and higher virulence than in vitro-grown populations, the latter being largely due to the non-sporulating fraction of the population, as shown by reinfection experiments with each subpopulation isolated via fluorescence-activated cell sorting. On the other hand, all subpopulations persisted similarly in the host and completed the infection cycle. Host-extracted subpopulations also showed increased tolerance to oxidative stress, consistent with an adaptation to conditions encountered within insect cadavers. Furthermore, competition assays revealed that non-sporulating bacteria from insect cadavers outcompeted sporulating cells, whereas the opposite was observed for in vitro-grown bacteria. In addition, spores produced in the host displayed reduced heat resistance but germinated more efficiently than laboratory-derived spores, highlighting environment-dependent properties which may affect transmission potential. Together, these results demonstrate that the host-associated ecological context drives functional differentiation within bacterial populations and modulates key traits linked to survival, competition, stress tolerance and persistence, emphasizing the importance of host-associated environments in structuring ecological properties of sporulating pathogens.

microbiology↗

bioRxiv2024

Translocations can drive expression changes of multiple genes in regulons covering entire chromosome arms

Translocations have largely been implicated in tumor development. However, beyond the consequences of aberrant gene expression near the breakpoint, their effects remain unexplored. In this work, we characterize the interplay between translocations, chromatin organization and gene expression using mantle cell lymphoma (MCL) as a model. We show that in vitro induced MCL-associated translocations can drive transcriptional changes at entire chromosome arms affecting multiple genes in a regulon-like fashion. Additionally, overexpressed genes in MCL patients are enriched in the exact same genomic regions, further underlining its potential relevance for lymphomagenesis. Moreover, we demonstrate a clear link between the translocation-induced transcriptional alterations and genome organization, with genes most susceptible to change expression residing in pre-existing long-range interacting loops spanning 50 megabases. The translocation places the strong immunoglobulin enhancer into this loop, allowing the spread of its regulatory potential over the entire affected chromosome arm. Finally, we show that translocation-induced effects mainly represent expression enhancement of genes already active prior to translocation formation, highlighting the importance of the epigenetic state of the cell in which this initial hit occurs. In summary, we show that translocations can induce ample, simultaneous gene expression changes affecting entire chromosome arms, representing an important new mechanism for tumorigenesis.

cancer biology↗

bioRxiv2022

A sporulation-independent way of life for Bacillus thuringiensis in the late stages of an infection

The formation of endospores has been considered as the unique mode of survival and transmission of sporulating Firmicutes due to the exceptional resistance and persistence of this bacterial form. However, the persistence of non-sporulated bacteria (Spo-) was reported during infection in Bacillus thuringiensis, an entomopathogenic sporulating Gram-positive bacterium. In this study, we investigated the behavior of a bacterial population in the late stages of an infection as well as the characteristics of the Spo- bacteria in the B. thuringiensis/Galleria mellonella infection model. Using fluorescent reporters coupled to flow cytometry as well as molecular markers, we demonstrated that the Spo- cells constitute about half of the population two weeks post-infection (pi) and that these bacteria present vitality signs. However, a protein synthesis and a growth recovery assay indicated that they are in a metabolically slowed-down state. Interestingly, they were extremely resistant to the cadaver environment which proved deadly for in vitro-grown vegetative cells and, strikingly, did not support spore germination. A transcriptomic analysis of this subpopulation at 7 days pi revealed a signature profile of this state. The expression analysis of individual genes at the cell level suggests that iron homeostasis is important at all stages of the infection, whereas the oxidative stress response seems of particular importance as the survival time increases. Altogether, these data show that non-sporulated bacteria are able to survive for a prolonged period of time and indicate that they engage in a profound adaptation process that leads to their persistence in the host cadaver.

microbiology↗